Symptomatic osteoarthritis (OA) of the knee and hip is common, the leading cause of disability and diminished quality of life among those 65 years of age and older, and responsible for a large proportion of the costs associated with joint replacement surgery and other direct and indirect health costs(I-10). As the population in the United States ages, this problem can only be expected to increase(9). Despite the high personal and societal costs of knee and hip OA, few modifiable risk factors for its occurrence or progression have been identified (11; 12). Heavy metals are ubiquitous, and exposure through drinking water, contaminated food, pesticides, and other means, is widespread in our society(13-18). This proposal introduces chronic metal exposures as novel, potentially modifiable risk factors for thc incidence and progression of knee and hip OA and its consequences. The study population is the Johnston County Osteoarthritis Project, an ongoing longitudinal study of OA in African-Americans and Caucasians in a rural county of North Carolina. The research plan adds the collection of additional biological specimens, namely whole blood and toenails, to the already funded examinations of the cohort to establish a resource for current and future examinations of multiple metals in OA and OA-related outcomes. Whole blood will be analyzed for lead at the Centers for Disease Control and Prevention, and toenails will be analyzed for mercury and selenium by instrtmaental neutron activation analysis at the University of Missouri-Columbia Research Reactor Center. Multiple logistic regression will be used to test associations between these metals and incidence and progression of radiographic knee and hip OA, knee and hip symptoms, and disability. By dovetailing this proposal with the funded cohort, costs are minimized, and efficiency and utility maximized.